Main Findings and Interpretation:
Our data demonstrate that pregnancies compromised by AFLP show exceedingly higher sFlt-1 and higher PLGF serum levels compared to pregnancies affected by HELLP syndrome. This biochemical phenomenon should focus our attention to diagnose or to rule out AFLP in women presenting with pregnancy-associated liver disorders. Moreover, this altered angiogenic pattern also underscores that AFLP and HELLP syndrome are two distinct entities. Similar to our findings, compared to pregnancies comprised to HELLP syndrome, altered angiogenic profile patterns were found in AFLP patients in a case reports as well as in case series.16, 17 These reports together with our findings are important novel insights, particularly since prospective studies will barely succeed due to the extremely low incidence of AFPL.5
Clinically it may be difficult to distinguish AFLP from other pregnancy-related diseases such as preeclampsia and HELLP syndrome due to the similarity of symptoms and laboratory features. However, a timely suspicion of AFLP is crucial for offering prompt diagnostic work up, delivery and intensive supporting care preventing deleterious maternal and neonatal outcomes. To date, applying the Swansea criteria reflects the best diagnostic strategy to identify AFLP. However, applying these criteria may delay the diagnosis of AFLP since they seem to be most efficient when the disease is already in an advanced state and life-threatening complications are occurring.22 Our data demonstrate that an s-Flt1 value >31100 pg/ml may be an additional parameter, if not even a key criterion, besides the Swansea criteria, to focus our attention on the differential diagnosis of AFLP. We postulate that sFlt-1 levels may herald AFLP prior to the presence of the Swansea criteria and before the patient is already severely ill. This gain of time may allow a coordinated peripartal management in a multidisciplinary setting.
Elevated sFlt-1 serum levels have been observed also in various non-obstetrical clinical situations including liver diseases.23 Our findings of very high sFlt-1 values in AFLP patients may be explained by the enormous inflammatory stimulus involving various organ systems leading to proteinuria and altered blood pressure. This common pathomechanism involving sFlt-1 may explain why AFLP share similar features with preeclampsia and in particular with HELLP syndrome, which in turn delay the diagnosis or the differentiation of these pregnancy complications.